Accelerated Porcine Wound Healing after Treatment with α-Gal Nanoparticles

Abstract

The α-gal epitope is a carbohydrate antigen that interacts specifically with the natural anti-Gal antibody--the most abundant antibody in humans. Anti-Gal/α-gal epitope interaction activates complement to generate chemotactic factors that induce rapid recruitment of macrophages. The authors hypothesized that α-gal epitopes on nanoparticles can accelerate wound healing by inducing rapid recruitment and activation of macrophages in wounds. α-Gal nanoparticles were generated from phospholipids, cholesterol, and α-gal glycolipids. α-Gal nanoparticle treatment of wounds was studied in 12 α1,3galactosyltrasferase knockout pigs. Like humans, these pigs lack α-gal epitopes and produce the natural anti-Gal antibody. Full-thickness wounds (20 × 20 mm) with tattooed borders were created on the back of pigs. α-Gal nanoparticles (10 or 100 mg) were topically applied onto the wounds. Saline-treated wounds served as control. Wound open surface area was measured every 3 to 4 days during dressing changes. Wounds from euthanized pigs were subjected to histological evaluation. Treated wounds displayed many more macrophages and increased angiogenesis than control wounds in the same pig. On day 10, wounds treated with 10 mg and 100 mg displayed 35 and 60 percent decreased open surface area compared with control wounds, respectively, and 80 and 90 percent less than control wounds on day 13 (p < 0.05). No keloid formation or no increase in scar formation was observed on day 60. α-Gal nanoparticle treatment of wounds accelerates macrophage recruitment, angiogenesis, and wound healing in pigs producing the anti-Gal antibody. As humans produce high titers of anti-Gal antibodies, this treatment may exhibit a similar beneficial effect in the clinical setting.